Alzheimer's - INTRODUCTION

Education Can Help Stave Off Alzheimer's Disease

Even with evidence of brain plaques associated with Alzheimer's disease, highly educated individuals manage to score higher on cognitive tests. Results from this study are published in the November issue of Archives of Neurology.

Currently there exists a popular notion - the "cognitive reserve" hypothesis - that people with greater thinking, learning, and memory capabilities can delay symptom of Alzheimer's disease even as the brain is changing. Since cognitive reserve is somewhat difficult to measure, researchers use education level as a proxy. "Adjusting for level of Alzheimer disease pathological burden determined at autopsy, greater education has been associated with better cognitive function during life," write Catherine M. Roe, Ph.D. and colleagues at the Washington University School of Medicine, St. Louis. "Education interacts with Alzheimer disease pathological burden such that a greater pathological burden is required to show an effect on cognition among persons with more education."

Between 2003 and 2008, the researchers analyzed 37 individuals diagnosed with Alzheimer's-like dementia and 161 individuals without dementia. Cognitive reserve measurements included education history as well as cognitive test scores. In addition, study participants received an injection of carbon 11-labeled Pittsburgh Compound B ([11C]PiB) prior to a 60-minute positron emission tomography (PET) brain scan. This contrast compound ([11C]PiB) has been shown to stick to beta-amyloid brain plaques that are linked to Alzheimer's disease, and thus researchers could identify the disease state in each patient.

Results of the study demonstrated that there were significant difference in the level of [11C]PiB uptake among patients with different years of education and cognitive test scores. For example, individuals with beta-amyloid plaques in the brain (organs that took up higher levels of [11C]PiB) showed increased performance on tests as education levels increased. For individuals without plaques, education was not significantly associated with cognitive scores.

"The results support the hypothesis that cognitive reserve influences the association between Alzheimer disease pathological burden and cognition," conclude Roes and colleagues. "Based on autopsy data, there may be a ceiling effect when extensive beta-amyloid pathological burden is present as in late-stage dementia of the Alzheimer type. Presumably, as the Alzheimer disease pathological burden increases, a greater proportion of highly educated participants reaches the threshold for dementia and the initial advantage provided by cognitive reserve decreases. Longitudinal imaging of beta-amyloid pathology in vivo will soon allow us to determine whether these inferences from cross-sectional studies are accurate."

Singles 'face Alzheimer's risk'

Being single when you reach middle age could mean more than having the house to yourself - it could increase your risk of dementia.

Swedish research, presented at a US conference, found that marriage or having a partner halved the risk of developing dementia.

Scientists believe social interaction between couples may ward off illness.

The Alzheimer's Research Trust said the results were worrying, given the high divorce rates in the UK.

The study by the Karolinska Institute suggested that the problem might be even greater for some people.

Divorcees who remained single, they noticed, had a trebled risk of dementia, while those widowed at a young age who stayed single faced a six times greater chance.

The research looked at 1,449 people from a Finnish database, who were asked about their relationship status in mid-life, then revisited 21 years later to see if they had developed dementia.

In total, 139 of them had some sort of cognitive impairment, and Alzheimer's had been diagnosed in 48 of these.

Even after other factors which might have an impact on dementia were adjusted for, the study consistently showed people with partners as less prone to the illness.

Advice for the single

Dr Krister Hakansson, who led the study, said: "Living in a couple relationship is normally one of the most intense forms of social and intellectual stimulation.

"If social and cognitive challenges can protect against dementia, so should living as a couple.

"This study points to the beneficial effects of a married life."

Rebecca Wood, from the Alzheimer's Research Trust, said that more research along these lines was urgently needed.

"These findings are particularly worrying for the UK - a society with a high divorce rate, marriage at an all-time low, and ageing population.

"This is the first study of its kind to examine the link between midlife marital status and dementia, adding to previous research suggesting that social interaction reduces dementia risk."

However, Susanne Sorenson, from the Alzheimer's Society, had some words of cheer for partnerless people.

She said: "Singletons shouldn't worry - there are many other ways to reduce your risk of dementia that don't involve popping the question.

"The best evidence is around eating a Mediterranean diet, exercising regularly and not smoking."

She also said that the findings were consistent with other research showing social interaction could be beneficial.

She added: "Whether it's reaching for the vacuum cleaner or going for long romantic walks, lifestyle factors associated with being married may also help."

Alzheimer's drug trial 'promise'

A drug once used to treat hayfever "significantly improves" symptoms in patients with mild to moderate Alzheimer's disease, research suggests.

Dimebon was once licensed in Russia as an antihistamine but was taken off the market when better drugs came along.

Now US researchers have found it can improve memory, behaviour and ability to conduct simple activities like eating in patients with dementia.

Experts were cautiously optimistic about The Lancet study findings.

In the trial of 183 people who all had untreated mild to moderate dementia, which was carried out in Russia, half were given 20 mg of dimebon 20 three times a day while the rest were given a dummy pill.

After six months, all were given tests such as memorising a list of words and performing simple tasks.

Those taking the drug scored four points lower on a scale designed to measure severity of Alzheimer's disease - meaning they were less badly affected.

Patients taking the drug scored better than they did at the start of the study but patients taking the placebo got worse over the six-month period.

In a smaller group of patients who continued with the trial for a further six months there was an even greater seven-point gap between those on dimebon and those on placebo.

It is not clear exactly how the drug works but it has been shown in animals to have a protective effect on nerve cells in the brain.

"Encouraging"

Study leader Dr Rachelle Doody, from Baylor College of Medicine in Houston, Texas, said the ongoing improvement seen in the study was particularly important.

Alzheimer's drugs already on the market are restricted for use in the NHS in those with moderately severe disease.

Rebecca Wood, chief executive of the Alzheimer's Research Trust, said: "The recent announcement of an additional phase III trial is encouraging.

"More research on this scale is desperately needed if we are to offer hope to the 700,000 people in the UK who live with Alzheimer's and other dementias."

The Alzheimer's Society agreed that more research was needed.

"These initial findings imply that dimebon could be more effective than treatments currently licensed for people with Alzheimer's, however this was a modest sized study."

Professor Robin Jacoby, an expert in psychiatry at the University of Oxford said there was a lot of interest in "old" drugs which had been used for other conditions as they would cost less to develop.

"On the face of it, these are fairly remarkable results.

"I would simply say that these things need to be treated with a great deal of caution and we want to see the results replicated."

A separate study by UK researchers also published in The Lancet reported that trials of vaccine developed to prevent progression of Alzheimer's disease have not been as successful as hoped.

Although the vaccine cleared the characteristic build up of clumps of protein in the brain of Alzheimer's patients it did not prevent neurological decline.

Exercise 'slows down Alzheimer's'

Being physically fit could hold back the advance of Alzheimer's disease, US researchers have suggested.

Their study, published in the journal Neurology, looked at 121 people aged over 60, around half of them in the early stages of the disease.

Those with Alzheimer's who were less fit had four times more signs of brain shrinkage than those who were fit.

The Alzheimer's Research Trust said other research showed exercise reduced the risk of dementia.

Some 700,000 people in the UK are living with dementia, with this number predicted to grow quickly over the next two decades, as the proportion of older people in the population increases.

Other studies looking at the relationship between dementia and exercise tend to focus on whether being active can reduce the risk of the condition developing in the first place.

Dr Jeffrey Burns, from the University of Kansas School of Medicine, said his was one of the first to look at whether exercise could affect the progress of the illness.

His volunteers underwent a treadmill test to see how fit they were and then their brains were scanned for shrinkage, which is one way of measuring the severity of their Alzheimer's.

Brain volume

While there was no relationship between brain size and exercise in people tested who did not have Alzheimer's, Dr Burns said the four-fold difference in those who did was evidence that exercise might help.

He said: "People with early Alzheimer's disease may be able to preserve their brain function for a longer period of time by exercising regularly and potentially reducing the amount of brain volume lost.

Doctors might be able to uncover high-risk patients using blood tests, they said in a US heart journal.

But other experts said the study did not yet support larger diet trials aiming to boost levels.

The relationship between levels of HDL, or "good", and LDL, or "bad" types of cholesterol is thought to be important in the development of other serious conditions such as heart disease and stroke.

Higher levels of HDL, in particular, are believed to protect against damage to blood supply caused by the narrowing of the arteries.

There is also evidence that "good" cholesterol can influence the laying down of the beta-amyloid "plaques" that are a distinctive feature in the brains of Alzheimer's patients.

Regular exercise and eating less saturated fat, while eating more "healthy" fats such as olive oils, can boost levels.

The researchers, from University College London and the INSERM institute in France, used data from the Whitehall II trial - a collection of thousands of civil servants, to see what influence it might have over memory within a five-year period.

They took blood samples at the start of the study, and gauged word recall with a simple test. That was repeated again at the end of the study.

The researchers found that people with low levels of HDL were 53% more likely to suffer memory loss compared with the people with the highest levels of HDL.

People with impaired memory have a much greater risk of going on to develop dementia later in life.

Early sign

Dr Archarna Singh-Manoux, who led the study, said: "Memory problems are key in the diagnosis of dementia.

"This suggests that low HDL cholesterol might also be a risk factor for dementia."

She said that doctors should be encouraged to monitor HDL levels in order to predict dementia risk.

However, an editorial in the same journal, Arteriosclerosis, Thrombosis, and Vascular Biology, by Dr Anatol Kontush and Dr John Chapman, from INSERM and the Universite Pierre and Marie Curie in Paris, said that the study did not prove that low HDL could cause memory loss, or high HDL protect against it.

"Unfortunate results in large interventional trials with dietary antioxidants suggest that we should remain cautious when proposing therapeutic intervention," they wrote.

Dr Susanne Sorenson, from the Alzheimer's Society, said HDL cholesterol was believed to transport harmful cholesterol from the arteries back to the liver to be degraded.

"This study shows that if there is not enough HDL to transport cholesterol and other lipids around the body, it can not only increase your risk of heart disease but also affect your memory and may increase your risk of getting Alzheimer's disease.

"We know that controlling cholesterol in midlife is important if you are to reduce your risk of developing vascular dementia later and this may also be important for the development of Alzheimer's disease."

New drug offers hope for Alzheimer's victims

An experimental drug to treat Alzheimer's Disease has been seen to be effective in trials with Alzheimer's patients.

The new drug bapineuzumab works by removing protein deposits from the brain that are associated with the disease.

In the study half of the 240 Alzheimer's patients were given the drug while the other half were given a placebo and the researchers say although the drug did not reach statistical goals it did prove to be relatively effective when given to patients diagnosed with the degenerative brain disorder.

Bapineuzumab is the latest drug to show promise in slowing down the progression of Alzheimer's and is one of 23 paths that drug company Wyeth is currently exploring in its quest for a treatment for the devastating disease.

The interim results showed that patients given the new drug showed less loss of brain volume among treated patients compared with those given a placebo.

Even though the study did not meet its primary goals because the drug did not appear to have the same effect on patients with the ApoE4 gene, the results are considered positive.

A phase 3 involving 4,100 Alzheimer's patients at 350 study sites will now go ahead and if approved, bapineuzumab could represent a significant advance over current Alzheimer's treatments, which can temporarily improve symptoms, but do not attack the underlying process.

Dual action Alzheimer's drug hope

Experimental drugs are being hailed as a potentially exciting step forward in the treatment of Alzheimer's.

The drugs, still in clinical trials, form a new class called gamma-secretase modulators (GSM).

A study in Nature shows they cut levels of the protein that forms the sticky clumps associated with Alzheimer's.

In addition, the international research team found the drugs boost levels of shorter pieces of the same protein which help to inhibit clump formation.

The clumps - or plaques - are formed of long pieces of amyloid beta protein, and are thought to cause the breakdown of communications between brain cells and lead to the development of dementia.

But shorter pieces of amyloid beta stop the longer pieces from sticking to each other.

The researchers compared the dual action of GSMs with that of drugs which help reduce the risk of heart problems by both lowering levels of harmful cholesterol, and raising levels of cholesterol which has a beneficial effect.

The researchers found that GSMs stick to amyloid beta protein that is already in the brain, preventing it from sticking together.

Amyloid beta is created by an enzyme that chops up a larger protein called APP.

But the latest research found that GSMs do not target APP, but the structure of beta amyloid itself.

The researchers said this was significant, as it showed beta amyloid can be targetted directly by drugs.

Researcher Dr Todd Golde, a neuroscientist at the Mayo Clinic in Jacksonville, said: "This broadens the notion of what drugs can do and therefore has wide-reaching implication for future drug discovery for many different disorders."

Human trials

Doctors are in the third and final phase of trials on human volunteers to test the first GSM, a molecule called tarenflurbil, branded as Flurizan.

Several more drugs in the class are set to enter human trials in the next year or two.

Rebecca Wood, of the Alzheimer's Research Trust, said: "This is an exciting step forward towards a potential new treatment for Alzheimer's disease.

"Scientists may be able to use this proof-of-principle research to develop a new class of drugs that specifically target this mechanism [the build up of plaques] in an effort to slow or prevent the development of Alzheimer's disease.

"Finding a way to prevent or delay the onset of dementia, even for a couple of years, would make a significant difference to the 700,000 people in the UK living with dementia and their families."

Alzheimer’s Disease, progressive brain disorder that causes a gradual and irreversible decline in memory, language skills, perception of time and space, and, eventually, the ability to care for oneself. First described by German psychiatrist Alois Alzheimer in 1906, Alzheimer’s disease was initially thought to be a rare condition affecting only young people, and was referred to as presenile dementia. Today late-onset Alzheimer’s disease is recognized as the most common cause of the loss of mental function in those aged 65 and over. Alzheimer’s in people in their 30s, 40s, and 50s, called early-onset Alzheimer’s disease, occurs much less frequently, accounting for less than 10 percent of the estimated 4 million Alzheimer’s cases in the United States. (Alzheimer’s Disease - Progressive brain disorder, Psychiatrist Alois Alzheimer in 1906)

Although Alzheimer’s disease is not a normal part of the aging process, the risk of developing the disease increases as people grow older. About 10 percent of the United States population over the age of 65 is affected by Alzheimer’s disease, and nearly 50 percent of those over age 85 may have the disease. (Alzheimer’s Disease - Progressive brain disorder, Psychiatrist Alois Alzheimer in 1906)

Alzheimer’s disease takes a devastating toll, not only on the patients, but also on those who love and care for them. Some patients experience immense fear and frustration as they struggle with once commonplace tasks and slowly lose their independence. Family, friends, and especially those who provide daily care suffer immeasurable pain and stress as they witness Alzheimer’s disease slowly take their loved one from them. (Alzheimer’s Disease - Progressive brain disorder, Psychiatrist Alois Alzheimer in 1906)